System and methods for embolized occlusion of neurovascular aneurysms

ABSTRACT

The present disclosure is related to an occlusion device having a mesh structure. The occlusion device configured to transition between a two-dimensional configuration and a three-dimensional configuration. In the two-dimensional configuration and at rest, the occlusion device is flat or planar. In the three-dimensional configuration, the occlusion device defines an internal volume.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/303,507, filed Nov. 20, 2018, which is a U.S. National Phase ofInternational Application No. PCT/US2017/034460, filed May 25, 2017,which claims priority benefit under 35 U.S.C. § 119(e) to U.S.Provisional Patent Application Ser. No. 62/342,135, filed May 26, 2016,titled SYSTEM AND METHODS FOR EMBOLIZED OCCLUSION OF NEUROVASCULARANEURYSMS, all of which applications are hereby incorporated byreference in their entirety.

BACKGROUND Field

This application is related to methods and devices for treatingneurovascular aneurysms.

Description of the Related Art

The worldwide occurrence of stroke is estimated to be in the vicinity of60,000,000 instances per year. The economic and social costs for strokesare enormous. While most strokes are fatal or debilitating, even mildstrokes often result in impairment that greatly diminishes quality oflife and independence while substantially increasing direct costs forhealthcare and daily living. Further, indirect costs such as lostproductivity, expanded burden on care provided by immediate family, andthe allocation of limited resources to rehabilitative therapy andconvalescence aggregate to create a significant unmet need for theprevention of stroke beyond the current standard of care.

While advances in medical science, standards of care, preventativeactions, and an understanding of the influences of personal lifestylehave improved in the field of stroke over time, the causes of stroke arecomplex and not fully understood in all instances. Stroke is dividedinto two categories: ischemic (loss of normal blood flow) andhemorrhagic (bleeding through blood vessel rupture).

A brain (cerebral) aneurysm is a bulging, weak area in the wall of anartery that supplies blood to the brain. If a brain aneurysm ruptures (asubarachnoid hemorrhage), it releases blood into the skull resulting instroke. Depending on the severity of the hemorrhage, brain damage ordeath may result.

The risk factors for formation of aneurysms are recognized to includegenetics, gender, age, race, elevated blood pressure, smoking, andatherosclerosis. In many cases an unruptured cerebral aneurysm may onlybe discovered during tests for another, usually unrelated, condition. Inother cases, an unruptured cerebral aneurysm will cause problems bypressing on areas in the brain. When this happens, the person may sufferfrom severe headaches, blurred vision, changes in speech, and neck pain,depending on what areas of the brain are affected and how severe theaneurysm is.

SUMMARY

At present there are three treatment options for people with thediagnosis of cerebral aneurysm: (1) medical (non-surgical) therapy; (2)surgical therapy or clipping; and (3) endovascular therapy or coiling.

Medical therapy is usually only an option for the treatment ofunruptured intracranial aneurysms. Strategies include smoking cessationand blood pressure control. These are the only factors that have beenshown to have a significant effect on aneurysm formation, growth, andrupture. Periodic radiographic imaging may be used to monitor the sizeand growth of an aneurysm. However, because the mechanisms of aneurysmrupture are not entirely understood, and because even aneurysms of verysmall size may rupture, monitoring cerebral aneurysms is an incompletesolution to meeting medical needs.

Surgical treatment of cerebral aneurysms has existed for more than 150years, and for more than 80 years the standard of care has included theuse of aneurysm clips which have evolved into hundreds of varieties,shapes, and sizes. The mechanical sophistication of available clips,along with the advent of the operating microscope in the 1960s have madesurgical clipping the gold standard in the treatment of both rupturedand unruptured cerebral aneurysms.

Surgical clipping remains an invasive and technically challengingprocedure whereby the brain and the blood vessels are accessed throughan opening in the skull. After the aneurysm is identified, it iscarefully separated from the surrounding brain tissue. A small metalclip is secured to the base of the aneurysm. The choice of a particularclip configuration is based on the size and location of an aneurysm. Theclip has a spring mechanism which allows the clip to close around eitherside of the aneurysm, thus occluding the aneurysm from the blood vessel.Normal blood vessel anatomy is physically restored by excluding theaneurysm sac from the cerebral circulation.

Endovascular techniques for treating aneurysms date back to the 1970swith the introduction of proximal balloon occlusion. Guido Guglielmi anAmerican-based neuroradiologist, invented the platinum detachablemicrocoil, which was used to treat the first human being in 1991.

Endovascularly delivered coils are soft wire spirals originally made outof platinum. These coils are deployed into an aneurysm via amicrocatheter that is inserted through the femoral artery of the leg andcarefully advanced into the brain. The microcatheter is advanced intothe aneurysm itself, and the microcoils are released in a sequentialmanner. Once the coils are released into the aneurysm, the blood flowpattern within the aneurysm is significantly reduced, leading tothrombosis (clotting) of the aneurysm. A thrombosed aneurysm resists theentry of liquid blood, providing a seal in a manner similar to a clip.

Endovascular coiling is an attractive option for treating aneurysmsbecause it does not require opening of the skull, and is generallyaccomplished in a shorter timeframe, which lessens the impact ofphysical strain on the patient. A limitation of coiling is that eventualcompression of the bolus of individual coils may compress over time andthus blood flow to the aneurysm may become reestablished. Additionally,not all aneurysms are suitable for coiling: (1) wide-necked aneurysmsrequire a support scaffolding (usually a stent) as a structural supportto prevent prolapse of the coil bolus into the blood vessel; (2)aneurysms that are located in the distal reaches of the neurovasculaturemay lie beyond the reach of current microcatheter sizing; and, (3)microcatheters filled with embolic coils are not always flexible enoughto navigate the highly tortuous and fragile anatomy of neurovascularblood vessels. As experience with coiling grows, the indications andpitfalls continue to be refined. Endovascular and coil technologycontinue to improve: endovascular adjuncts, such as intracranial stents,are now available to assist in coiling procedures; the original platinummicrocoil has been refined with ever-improving features such asbiological coating and microengineering for efficiency in deployment.

More recently, endovascular devices alternative to coils have begun toopen further options for the treatment of aneurysms. Blood flowdiversion without coils may provide a less expensive, more efficient,and more adaptive means for the treatment of aneurysms.Nickel-titanium-based (NiTi) flow diversion structures provide furtheroptions for physicians and patients. At present, laser cut hypotube orbraided wire form the structures from which flow diverters are made.Laser cut hypotubes require complex manufacturing and have limitationsin the degree of expansion deformation that they can tolerate.Alternately, braided wire forms are much less complicated tomanufacture, can tolerate substantial expansion deformation, but offervery limited control of structural porosity due to the localizedunconstrained movement allowable between wires that are not mechanicallybound together.

Therefore, a substantial need exists to increase minimally invasive andcost-effective solutions to improve intracranial access using systemsand methods to control the risk and effects of hemorrhagic strokethrough means of very small, highly capable, and reliably producibleinterventional tools and implants.

Some aspects of the present disclosure provide the means and the methodsfor treating cerebral aneurysms via a catheter-based, minimally invasiveinterventional system that includes a blood flow diverting implant thatis placed within the aneurysm sac.

Some aspects of the present disclosure include deploying the implantfrom a microcatheter having an outer diameter of 0.027 inches or less,for example 0.021 inches or less at the distal working area of themicrocatheter. Manufactured with polymer, metal and polymer, polymer andthin film, polymer and integrated braided material for torque control,and integrated tether mechanism or tether line for release of theimplant. The release may be completed by mechanical energy, or absorbedor by delivered energy such as thermal or electrical or by environmentalenergy from thermal body temperature transfer.

Some aspects of the present disclosure provide a restraint forrestraining, and optionally recapturing, an implant so as to aid in theaccurate positioning and deployment of an implant in situ.

Some aspects of the present disclosure are directed toward an implantfor treating an aneurysm that is a blood flow diverter (e.g., occluder)comprised of thin-film NiTi. When deployed, the NiTi implant may be inthe martensitic (shape memory) state, the austenitic (superelastic)state, or a mixture of both or may be a multilayer of several filmcompositions. For example, a deployed NiTi implant is more austeniticthan martensitic in situ.

Some aspects of the present disclosure are directed toward an implantfor treating an aneurysm that is a blood flow diverter (e.g., occluder)comprised of an acceptable biocompatible metal including, but notlimited to, biocompatible stainless steel, tantalum, tungsten, titanium,TiNi, platinum, or combinations or multilayers thereof. The metal shallbe of a medical biocompatible material that may be delivered into theaneurysm utilizing balloon, wire or assisted delivery by other means, orencapsulated and then released.

In some configurations, the self-expanding implant may include NiTithin-film, wherein the film is initially formed in a substantially flator planar, two-dimensional form and then subsequently shaped into athree-dimensional form prior to incorporation into a catheter. Inthree-dimensional form, the implant may be a sphere or other enclosed orsemi enclosed structure made of a hollow, semi hollow, or fully-filledthin film body. The surface area may be many times greater than volumewhen conformed for delivery to the specific site of treatment.

The thin film NiTi implant may be combined with additional wire, foil,and/or thin film elements either before or after shaping to provideadded structural elements. The NiTi material would shape within therange of body temperature from as low as a set temperature 34 degreescentigrade and as high as 40 degrees centigrade.

In some configurations, the deployed implant may include a portion thatconforms to the opening at the neck of an aneurysm.

In some configurations, the deployed implant may include a bottomportion that diverts blood flow away from the neck and sac of ananeurysm and is comprised to include one or more additional portionsthat fill at least some of the sac of an aneurysm.

In some configurations, the implant may include NiTi thin film, whereinthe film is initially formed in a partially three-dimensional form andthen subsequently further shaped into a final three-dimensional formprior to incorporation into a catheter.

In some configurations, the implant may include NiTi thin film, whereinthe film is initially formed at least partially or at leastsubstantially in three-dimensional form prior to incorporation into acatheter.

Some aspects of the disclosure are related to implants including NiTithin film, wherein the film may be comprised of a regularly repeatingpattern of meshed structures (e.g., regularly repeating porosity),wherein the meshed structures may be any pattern that optimizes thefilm's ability to expand from a highly compressed state that can loadedinto a catheter to a substantially expanded state after release into theaneurysm while also optimizing the degree of localized stress and strainexperienced by elements of the mesh.

Some aspects of the disclosure are related to implants including NiTithin film, wherein the initial flat or planar form of the device may beshaped such that it can be formed into a three-dimensional shape asdesired for deployment into an aneurysm prior to incorporation into acatheter and then unfolded into a different three dimensional shapeconducive to loading into a catheter, such that upon deployment from thecatheter the device returns to the first shape.

Some aspects of the disclosure are related to implants including NiTithin film, wherein the film may be comprised of a regularly repeatingpattern of meshed or perforated structures, wherein the structures maybe any pattern porosity that optimizes the occlusive performance of thestructure.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments are depicted in the accompanying drawings forillustrative purposes, and should in no way be interpreted as limitingthe scope of the embodiments. Furthermore, various features of differentdisclosed embodiments can be combined to form additional embodiments,which are part of this disclosure.

FIG. 1 shows a schematic view of the interventional system of thepresent disclosure in a representative access pathway to a cerebralaneurysm.

FIG. 2A shows a representative example of an aneurysm, located laterallyalong the length of a blood vessel, with a representative example of animplant located therein.

FIG. 2B shows a representative example of an aneurysm, located at thebifurcation of a blood vessel, with a representative example of animplant located therein.

FIGS. 3A-3E show a schematic depiction of an implant embodiment duringits forming process.

FIGS. 4A and 4B show a schematic depiction of another implant embodimentduring its forming process.

FIGS. 5A-5E show a schematic depiction of yet another implant embodimentduring its forming process, and the compression process prior tocatheterization.

FIGS. 6A and 6B depicts a schematic representation of another embodimentof a NiTi thin film mesh structure and a unit cell thereof.

FIGS. 7A-7D depict a schematic representation of embodiments of NiTithin film mesh structures in a collapsed state and in an expanded state.

FIG. 8 shows a schematic representation of an embodiment of a NiTi thinfilm mesh structure in a substantially planar state.

FIG. 9 depicts the embodiment of FIG. 8 during the three-dimensionalforming process.

FIG. 10A shows a schematic depiction of an exemplary embodiment of arestraint at the working end of the system shown in FIG. 1 .

FIG. 10B shows a schematic depiction of the restraint of FIG. 10A in usedeploying the implant of FIGS. 3A-3D.

FIG. 11 shows a schematic depiction of an implant embodiment in situ.

FIGS. 12A and 12B show a schematic depiction of an implant embodiment ina planar state and a formed three-dimensional shape.

FIGS. 13A to 13D show yet another implant embodiment in a planar stateand a partially cylindrical shape.

FIGS. 14A to 14D show yet another implant embodiment in a planar stateand a partially spherical shape.

DETAILED DESCRIPTION

As has been previously explained herein, there remains a need forfurther advancement in minimally invasive interventional treatment ofcerebral aneurysms. The tortuous anatomy, small vessel diameter, anduniquely delicate anatomy of the neurovasculature provides for aparticularly challenging set of constraints in which an interventionalsystem must operate. There is little room for error given that even thesmallest unintended consequences of an error often result in significantnegative consequences for a patient.

Delivering the Implant

When treating a cerebral aneurysm, a system should be able to navigatethe access pathway to the target site. As is shown in FIG. 1 , a typicalmethod is to access a femoral blood vessel at location 104 and traverseaccess pathway 105 through the heart and into the cranial cavity to ananeurysm location 106 that is substantially distal from access location104. This is done with known interventional techniques which may includesystem 100 of the present disclosure comprised of a complex set offeatures which may be subdivided into principal functional subsystemscomprised of control handle 101, catheter body 102, and catheter distalworking end 103 (further containing an implant).

System 100 should possess enough rigidity to traverse the torso and itscirculatory system along pathway 105, and then the more distal,tortuous, delicate and small diameter vessels of the cranium untiltarget aneurism location 106 is reached. System 100 should be able totrack to location 106 along pathway 105 through a micro guide catheter,over a guide wire, or on its own via natural shaping of catheter body102 and/or steerable control from the proximal end via control handle101.

Access to more distally located targets becomes limited by the size andstiffness of catheter working end 103, which in turn may be limited bythe physical aspects of the implant contained therein. A solution tothis problem of limitation is to provide an implant structure thatprovides the simultaneous abilities of compressing to a very smalldiameter, below 0.021 inches, e.g., smaller than 0.019 inches, whileremaining flexible in its compressed state, and then being able toexpand to many times its compressed diameter in order to fixate andperform safely in situ.

Tracking, manipulation, sheath control, compatibility with guidewiresand other access tools and techniques are incorporated into the assemblyand use of catheter system 100. The implant loaded into working end 103may be radially compressed and/or folded similar to the way thatangioplasty balloons and stents are loaded to reduce the profile of thedistal section of a polymer delivery system, where a guide wire lumenand an outer lumen and a working end 103 where the implant is coveredwith a sheath. The sheath may be retracted releasing the implant totarget site 106 or the implant may be pushed or manipulated from controlhandle 101 at the proximal end of catheter system 100 using a mandrel,guide wire or braided shaft, or other such means providing pushableforce transmission a columnar strength through tortuous anatomy suchthat the load bearing unit is able to effect the desired action atworking end 103 to deliver an implant to target site 106.

Additionally, catheter system 100 may also integrate a tethered lineconnected to the implant at working end 103 and extending proximallythrough catheter body 102 to control handle 101 which enabling cathetersystem 100 system to recapture or reposition the implant prior tocompleting deployment at target site 106.

One example of tethering means may include a tether comprised of alubricious polymer tied by a slip knot method where one end of the lineis integrated with the catheter body 102 and the second end is able tobe controlled an communicated with by the user at control handle 101.

Another example of tethering means may include dissoluble material thatinteracts with blood or fluids and breaks down over the standardduration of the implant procedure such that the implant is released whenthe tether line is broken by erosion, the application of force, or both.

Additionally referring to FIGS. 10A-10B, yet another example of a tetheror restraint may be comprised of a mesh thin film or braided material108 connected to a delivery wire 107 inside of catheter body 102 atworking end 103, wherein delivery wire 107 and restraint 108 may bejoined using any means of attachment known in the art, such as:energy-based fusion (such as heat); chemical bonds and adhesives;mechanical means such as crimping, interference fits, swaging, pressfitting; and the like. A suitable connection joint should be able towithstand tensile loads equal to or greater than 0.1 Newtons.

Restraint 108 may further double as a snare which may be configured as acone (as shown by example 108), a collet, a leaflet of 3 sides, or othersuch structures that expand and collapse with minimal outward force butshall open when released and/or not bound by the constraint of workingend 103. The material of restraint 108 in such application may be of anymedical-grade engineering material such as metals, polymers, textilesand the like, for example NiTi and further optionally being at leastpartially in the austenitic phase.

As is illustrated by FIG. 10B, restraint 108 may be compressed into theinside diameter of working end 103 of catheter body 102 of deliverysystem 100 while maintaining a sufficient grip on implant 300 stored anddeployed from the inner diameter of working end 103. As is shown, upperportion 301 and middle portion 302 are in mid-deployment while themajority of restraint 108 and lower portion 303 of implant 300 remainconstrained inside catheter body 102 until delivery wire 107 is advanceddistally to further expose them. Optionally, an implant may be comprisedto include a structure to mechanical interface with restraint 108through structures such as: a formed nipple; a shaped eyelet; a noduleshape; round or non-round protrusions or recesses. While restraint 108and implant 300 are constrained by working end 103, both are in a stateof mechanical interaction that allows the implant to not be fullyreleased and deployed to target location 106. The ability to recapture,reposition, or otherwise positionally manipulate an implant prior tobeing fully deployed from working end 103 to target site 106 isparticularly advantageous for vascular interventional procedures wherethe accuracy of a permanent implant is of critical importance and thephysician is limited by the tools that may be used in such minimallyinvasive methods. When doubling as a snare, restraint 108 should providesufficient retention force on the implant at working end 103 so as toprovide the structural strength to allow for recapture of an implantuntil it is released, with up to as much as two-thirds of the implantbeing exposed from working end 103 while maintaining recapturability.

The implant may also be non-tethered and placed at the end of a push rodand affixed thereto via a chemical bond, such as a layer of polymerbonded by heat or chemical, allowing for sufficient attachment forceduring the delivery and deployment procedure but is releasable uponerosion, the application of force, or both.

The delivery system may have an attached mesh, cage, or sheath likematerial made from thin film NiTi, braided metallic wire ofbiocompatible material or braided polymer and connecting to an innershaft and the ID of the outer shaft which when both are manipulated theinteraction in two directions cause the release of the implant from itsconstrained state into the selected site of delivery.

The outer shaft may also be maintained stationary in the selectedposition and only the inner shaft is moved to release the implant fromits constrained position. The outer and inner shaft may also be heldstatic in selected positions and a third shaft of smaller configurationthan the inner ID be used as a pusher shaft to release the thin filmfrom its constrained condition. The outer and inner shaft may also bestatic in selected positions and the temperature change enables the thinfilm to free itself from its constrained position and spring forwardinto the delivery site.

All of these possible configurations shall be compatible with othercommon methods of treatment to ensure the product is able to be usedwithout limitation. Such treatments include gamma radiation, EOsterilization, and E-Beam. These shall not hinder but may complement thecomplete device in its function to deliver the implant from itsconstrained configuration.

Loading the implant into the delivery system may be done to enable thecompete loaded device to be sterilized as a fully assembled item or thesterilized implant may be provided in a loading device—similar to asyringe (but with a augmented cannula) where the sterilized NiTi implantis loaded into the delivery system distal end at the time of use thusenabling delivery to the desired treatment site within the body by thedelivery system.

The occluder may be retained in an outer lumen or double lumen with thedelivery system push rod in tracking to the delivery site and then thepush rod shall be moved in reference to the lumen for release.

Methods of Delivering an Implant

The occluder shall be able to loaded into a delivery system that shallbe of specific length based on the vascular system access location toreach the location of the aneurysm or area of disrupted blood flowcreated by a primary artery with a non-uniform wall (a disproportionatewall caused by disfiguration of the artery) while still maintaining theblood flow. The Thin Film implant device is compressed to comply withthe inner diameter of the delivery system and may be carried on a rigid,semi-rigid, or completely flexible spine system made from differentimplantable materials or similar or equivalent implantable material ableto contain and release the device, as depicted in FIGS. 5C, 5D, 5E and10A.

At this location, placement of an occluder in the primaryartery/capillary to fill the disproportionate wall volume and enablingthe human body natural endothelization, or clotting, to clot and sealoff the disproportional wall section from the primary vessel.

The retention of the occluder in the delivery system shall be achievedby an interference fit to the inner push rod and the extended areacreated by a shape material which can be integrated to the innerdelivery push rod and with the occluder mated with the delivery push rodsuch that when finished crimping the distal end of the delivery systempush rod shall maintain a retention, measurable by the tension force topull the occluder from the delivery system push rod and when thedelivery push rod end, retaining the occluder, achieves desired andmaterial set temperature, the delivery retention shall open allowing therelease of the occlude. The delivery may be an action of 2 opposingmotions, with dual action vectors, to release the implant from itscradling mechanism in the delivery system or a simple single action,mono directional vector.

Implant

Any of the implants described below can be used with the deliverysystems and methods described above.

Referring now to FIGS. 2A and 2B, cerebral aneurysms come in differingtypes. Two representative examples are the aneurysm 106(a) formedlaterally along the side of neurovascular vessel 107, and the aneurysm106(b) formed at the bifurcation of neurovascular vessel 108 into branchvessels 109 and 110. In either case, an implant 200 representative of atleast one aspect of the present disclosure is shown in situ in itsdeployed and fixed state. Any of the features described with respect tothese representative implants can apply to any of the embodimentsdescribed below.

Blood flow diversion is an aspect of implant 200, which does not requirean absolutely solid surface in order to be effective. The ideal resultis to provide a structure that is supple enough to avoid placing harmfulpressure on the inner wall of the aneurysm sac 106(a) or 106(b), whileoccluding blood flow within the sac, and while diverting blood flow backinto the healthy normal pathways of the native vessel(s), and whilehaving enough mechanical strength to safely fix in place.

A fine mesh is well suited to such requirements, where the porosity ofthe mesh (e.g., open area of each pore) may range from about, 50 micronsto about 1500 microns, and most ideally about 100 microns to about 1000microns. Each of the implants described herein can include a meshstructure for blood flow diversion is that the mesh be of asubstantially uniform porosity in the two-dimensional configuration andthe three-dimensional configuration. When transformed from atwo-dimensional configuration to a three-dimensional configuration, thepore size or open area of each pore in the three-dimensionalconfiguration changes less than 20% (or less than 15%, or less than 10%,or less than 5%) than the pore size or open area of the same pore in thetwo-dimensional configuration. In each of the two-dimensionalconfiguration and the three-dimensional configuration, there is lessthan 20% (or less than 15% or less than 10% or less than 5%) variationbetween the pore size or open area of any two openings. In each of thetwo-dimensional configuration and the three-dimensional configuration,there is less than 20% (or less than 15% or less than 10% or less than5%) variation between the pore size of any opening and the mean poresize of the entire porosity. In some configurations, every pore andopening has a uniform size in the two-dimensional configuration and/orthree-dimensional configuration.

Currently, meshes of this nature are constructed from braided NiTi wire.However, a braided structure inherently allows the individual wires ofthe braid to move past one another such that the unit cells formed byindividual braided strands are inconsistent (uncontrolled) in size dueto deformations that naturally occur during shaping and/or handlingprior to deployment. Additionally, as layers of wire stack up in acompressed and catheterized braided implant, stiffness develops that maylead to limitations in distal vascular access and/or further localizeddeformations of an implant's braided unit cells.

These problems may be improved by creating a mesh structure from amonolithic material which may include any medical grade material (metal,polymer, etc.) that is suitable for meeting the competing criteriapreviously described. One particular material is NiTi which has beenformed in a film-like thickness and patterned to have a mesh structuretherein. The thin film may further be created by using film depositionand patterning processes. Moreover, intraluminal devices such as stentsrequire aggressive antiplatelet therapy and are associated with higherthromboembolic (TE) complication rates. Intravascular flow disrupters(IFD) are currently braided-wire devices designed to achieve flowdisruption at the aneurysm neck without placing material in the parentvessel and without the need of antiplatelet therapy. In addition to thelimitations of braided wire structures previously described herein,better system performance may be achieved by producing IFDs made fromNiTi thin films. As opposed to a braided structure, a thin filmstructure may be patterned such that the mesh is either symmetricallyrepetitive or otherwise preferentially patterned in an asymmetric way soas to account for surface performance optimization for a threedimensional shape based on the portion against the wall of the aneurysmsac and the portion in contact with, and diverting, blood flow. One ormore of these thin film features can be applied to any of the implantembodiments described herein.

The implants described herein can transform from a first, substantiallyflat or planar configuration to a second, three-dimensionalconfiguration having an internal volume. The implant can be formed froma continuous or monolithic sheet (e.g., thin film layer). The continuousor monolithic sheet can have a substantially uniform thickness. Thethickness can be less than or equal to 0.005 inches, less than or equalto 0.003 inches, less than or equal to 0.002 inches, or less than orequal to 0.001 inches.

The implant can be patterned with a structural mesh that maintainssubstantially uniform porosity. The implant can be shape set to achievethe designated configuration (e.g., spherical, partially spherical,elliptical, etc.) with a major and minor diameter, or a three-axisdiameter with equal diameters, or two equal diameters and one unequal,or two unequal diameters, or all unequal diameters, that when releasedinto the treatment site shall optimally fill the aneurysm and fill,block, or shield the neck transition (primary artery to aneurysm voidfrom the same vessel wall) to the aneurysm space. In thethree-dimensional configuration, the implant has sufficient structuralsupport to maintain its shape in a fluid pressure environment equivalentor greater to the level of high blood pressure (e.g., 3/2 psig; similarto diastolic/systolic in mm of HG for high blood pressure).

The substantially flat or planar configuration can include rounded,circular, elliptical, cone, and other polygonal segments. Threedimensional configurations may comprise all the facets of the 2dimensional configurations with the introductions of additional axes atdefined points as determined by how the film is manipulated prior toshape setting to create a three dimensional structure.

The implants described herein can be compressed into a smallconfiguration by crimping in a circle or folding as a two fold, threefold, four fold and/or more folds, similar to angioplasty balloonfolding, without significantly work hardening the material to change itsdesired properties for filling and acting as the neuro-aneurysm filler.

Referring now to FIGS. 3A-3C, an example of a thin film NiTi meshstructure 300 is shown. FIG. 3A shows a deposited and patterned sheet ofthin film NiTi in a substantially flat or planar state. An upper segment301 and a lower segment 303 are joined by connecting segment 302.Segments 301 and 303 may be symmetrical to one another or asymmetrical.The representative example in FIGS. 3A-3C is symmetrical but will beappreciated as including the dimensional variations that wouldaccommodate asymmetry. In the example, implant 300 is comprised of amesh having the segments described. Segments 301 and 303 are circular,having a circumference of “C”, and are connected by element 302 having alength “L” which is equal to C when measured at the points of outersurface tangency between elements 301, 303, and 302.

As the substantially flat or planar configuration of FIG. 3A is shapedinto the three dimensional shape shown in FIGS. 3B and 3C, it can beseen how a planar structure evolves through shaping. Shaping may beachieved through the combination of mechanical deformation and heattreatment. Very often, successive incremental steps are required totransform the structure from its initial to its final shape. The formingsteps and heat treatment process are a function of the strains involvedin forming and the desired final mechanical properties of the threedimensional structure. In this example, structure 300, when in itscompressed state, forms the spheroid shape of FIG. 3C while continuingto possess flexibility (e.g, some degrees of freedom offered by thesegmented design), as illustrated in a not-fully-compressed state shownin FIG. 3B. While a spheroid shape is used for example purposes, otherthree dimensional shapes, such as partially spherical shapes, andsegment combinations may be used to achieve the concept of this aspectof the present disclosure.

Referring now to FIGS. 12A and 12B, another example of an implant 1200which, when shaped to a three-dimensional configuration, may include ahemispherical bottom portion 1201 (omitting a hemispherical top portion)and include one or more filler portions 1203 and 1205, respectivelyinterconnected by portions 1202 and 1204 terminating and at leastpartially filling hemispherical portion 1201 shaped to cover theaneurysm neck entrance, where bottom portion 1201 is greater in diameterthan the aneurysm neck entrance. Bottom portion 1201 may be shaped asany hemispherical shape or shape combination, such as: largest planarsection 1205 is described by a cord; having a major and minor diameterequal or unequal, with a deflection from an axial centerline to theouter tip of the cord shaping the component to act as a base internalcap at the arterial vessel neck to the entrance of the aneurysm base;and the like.

Referring now to FIG. 11 , the optional addition of an exteriorcontoured portion 1102 may be continuously connected or fused to theimplant which may be configured to cover the aneurysm neck. In theexample of FIG. 11 , implant 1100 is situated inside aneurysm location106(c) along blood vessel 111, having aneurysm neck 112. The upperportion 1101 of implant 1100 is monolithically attached to lower portion1102. For the purposes of illustration, lower portion 1102 is shown as asaddle-shaped element, however, lower portion 1102 may be any shape thatconforms to at least a portion of the contour of neck 112 such thatlocalized blood flow diversion and stability are provided for in thespirit of the present disclosure. Furthermore, implant 1100 contours maybe shaped to the major/minor of the primary vessel and/or aneurysm, andeven the radial diameters of not just the aneurysm 106(c) but even neck112 to optimize the blood flow diversion.

In some of the implant shape variants, implant surface area may be manylarger than implant volume, for example, in the case of a spheroid, sucha surface area to volume relationship may be managed by the major andminor diameter of the spheroid where the major diameter may be as smallas 0.1 mm and the minor diameter may be as small as 0.1 mm (e.g.,spherical, partially spherical, elliptical, etc.). The surface area of asurface of the implant may be many times greater than volume, such thatportions of the implant overlap each other. The surface area of asurface (one side) of the implant can be at least 1.5 times greater (orat least 2.0 times greater, or at least 2.5 times greater, or at least3.0 times greater) than an internal volume formed when the implant is inthe three-dimensional configuration.

In any of the implant shape variants, various locations along thesurfaces of the implant may also include varying thickness at designedpoints on the inside or outside surface to provide structural supportfor radial strength or the implant. For example, hemispheres, disks andcords may be shaped with grooves, channels, or rails to add to thestructural strength in the radial and axial directions for improveddevice stiffness and load carrying ability once deployed in situ.

In any of the implant shape variants, there may be reinforcing portionswith no porosity. The reinforcing portions may extend at least partiallyor entirely around a perimeter of the implant. The reinforcing portionmay extend at least partially or entirely across a width or length ofthe implant (e.g., similar to struts). The reinforcing portions mayinclude a same thickness as the porous or mesh portions of the implant.

FIGS. 3D and 3E show an exemplar NiTi thin film made in the form ofFIGS. 3A-3C. The spheroid implant 300 may be made with one sheet ormultiple sheets layered to increase thickness, where shaping can becompleted with the sheet(s) layered onto a shaping tool for heattreatment.

In addition to thin film mechanical properties such as material phaseand phase transition temperature, residual strain, and mesh structuralpattern, further mechanical stiffness may be derived from film thicknessfrom layering of two or more thin film layers, and from formedstiffeners such as pleats or spines and the like. The spines can be usedto elongate the thin film material to act as a compression mechanism inreducing the shape set to a different shape that can be placed in alumen of smaller size then the sphere for delivery to the determinedartery site.

Referring now to FIGS. 8 and 9 , another exemplar embodiment is shown.An implant 900 is comprised of a thin film mesh in a substantially flator planar form having a plurality of segments that may be shaped into athree dimensional form such as a spheroid. An upper segment 901 isjoined to a middle segment 903 by connector segment 902, and a lowersegment 905 is joined to a middle segment 903 by connector segment 904.Any number of middle segments and connectors may be used to fill andstiffen the central volume of the implant 900, here, a single middlesegment 903 with connector segments 902 and 904 are shown for simplicityof communication. Any variety of shape combinations or permutations maybe employed, such as: equal major and minor diameters, or unequal majorand minor diameters, and the like. The one or more inner segments mayalso be of any other geometric shape that acts as a volumetric fillerwithin the implant and the aneurysm sac. Most preferably volumetricfilling is preferentially positioned nearer the aneurysm neck. In otherembodiments, the volumetric filler is a separate component (e.g., acoil).

In FIG. 9 a multi-piece shaping tool is shown shaping upper segment 901,connector segment 902, middle segment 903, connector segment 904, andlower segment 905 into a spheroid shape. A top, outer tool piece 906sandwiches segment 901 over hemispherical forming piece 907. Connectorsegment 902 serves as the bending transition to middle segment 903 whichis sandwiched between tool pieces 908 and 909. Connector segment 904serves as the bending transition to lower segment 905 which issandwiched between lower hemispherical forming piece 910 and bottomouter tool piece 911. The various pieces of the forming tool may besecured together via a threaded hole and screw, an outer clamp, or othersuch means of mechanical securement prior to the tool and implant 900being heat treated for shape setting. Heat treatment may occur in avacuum or non-vacuum inert environment (inert created by using nitrogen,argon or helium gas), fluidized bed, molten salt bath, furnace, or thelike, heated to the necessary shaping temperature. For example, theshape setting temperature may be greater than 450 C with subsequentquenching in a cooler media so that the thin film material takes on a 3dimensional shape. This process may be assisted by wrapping the thinfilm around tooling or constraining it with wires or other structuralelements to conform it to the desired final shape during the formingprocess. A post descaling or passivation process may be implemented tooptimize the surface finish and minimize the possibility of fraction orcorrosion.

Corrosion resistance and biocompatibility may be enhanced by placementof an inert micro layer of metallic or non-metallic material at anatomic level, or greater thickness, to ensure of a surface passivationthat is robust and can resist corrosion or leach ions into the bloodsystem. The final outer surface may have a final surface finish ofmaterial that will be inert to the body and resist corrosion by placingan ionic layer of (Ti) titanium, (Pt) Platinum, (Pd) palladium, (Ir)iridium, (Au) Gold, or other biocompatible metals or may be passivatedby the formation of a surface titanium oxide layer. Stainless steel thinfilms shall be consistent with the medical grade ISO standardrequirements of 316, 316L, 316 LVM, 17/7 and any other long term implantmaterials.

Referring now to FIGS. 4A and 4B, an implant embodiment 400 is shown asbeing comprised of a thin film mesh 401 formed in a substantially threedimensional state with open ends 402 where a target mandrel would bepositioned during the film deposition and patterning processes. Uponfurther shaping and expansion of mesh 401, implant 400 takes on a threedimensional form of the final implant, a spheroid for example, wheresome evidence of open ends 402 may remain after shape setting. Referringnow to FIGS. 5A-5E, an implant embodiment is described during itsforming process, and, during the compression process prior tocatheterization.

Implant structure 500 begins in a substantially two dimensional flat orplanar form comprised of a plurality of struts with eyelets collectivelyreferred to as element 501 which commonly terminate at a central eyelet501′, the strut structure 501 and 501′ being layered over and attachedto a thin film mesh 502. Common structural eyelet 501′ and individualstrut eyelets 501 may be used as part of the three dimensional formingprocess.

A three dimensional forming tool 510, which for purposes of illustrationis a sphere but may be of any shape so desired, may be comprised toinclude a central passageway 511 through which wire 512 may be passed.As is shown in FIG. 5C, the hole formed by central eyelet 501′ may bepositioned concentrically with the opening of passageway 511 such thatwire 512 may be passed through central eyelet 501′ and into passageway511 in shaping tool 510. The plurality of struts with eyelets 501 may beforced to conform around the outer surface of forming tool 510 andsecured in place by positioning the plurality of strut ends with eyelets501 over the opening of passageway 511 on the opposite end of formingtool 510 before wire 512 is then positioned through eyelets therebysecuring them in position to assume a three dimensional shape. Thin filmmesh 502 being joined to the plurality of struts 501 also follows thecontour of forming tool 510. The joining of mesh 502 to the plurality ofstruts 501 may be accomplished by laser welding, resistance welding,mechanical crimping, clipping, riveting, and the like, or, may beattached after shape setting heat treatment through means of adhesion bybrazing, or chemical bonding. Alternatively, mesh 502 and struts 501 maybe formed as an integrated thin film structure.

FIGS. 5D and 5E show schematic representations of another embodiment. Anoptional s-shaped wire segment 503 may be included in the structure ofimplant 500 to facilitate collapsing its structure for insertion into acatheter. Wire 503 may be comprised of any implant-grade material, withone choice being a wire comprised of shape set NiTi which may be isinserted down the center of implant 500 and fixed in place with metalclips 504 on either end of the plurality of struts 501 and centraleyelet 501′. The clips may be of a metal or metal alloy with good x-raycontrast to assist in visualization of the location of the implant whileit is being inserted into position, such materials may be selected fromany of the groups known in the art such as noble metals, tantalum,palladium, bismuth, and the like. Where galvanic corrosion is ofconcern, an insulating layer may be used between the surfaces of clips504 and the surfaces of elements 501 and 501′ so as to prevent theformation of a galvanic couple. The size of clips 504 should fit intothe inner diameter of the microcatheter that will be used for deliveryin vivo. The expanded, three dimensional shape of implant 500 may thenbe diametrically collapsed by pulling on central wire 503 to stretch theplurality of struts 501 and mesh 502 along the central axis so that itforms a thin oblong structure that will fit into the catheter. When theimplant 500 is released from the microcatheter into the aneurysm sac,the entire structure of implant 500 will spring back into its threedimensionally formed shape.

Additionally, a radiopaque marker band (or clip 504) may be made bycrimping, bonding or fusing to mesh 502. Mesh 502 may also be configuredinto a small ball and fused together by energy that initiates a moltenstate of the material of mesh 502 but controlled by the intensity ofenergy delivery through means such as laser, acoustic or vibration, andthe like.

Reference is now made to FIGS. 6A and 6B, which depict a schematicrepresentation of an embodiment of a NiTi thin film mesh structure and aunit cell thereof. The geometry of the NiTi mesh and its mechanicalproperties are important factors influencing how well the implantperforms its variety of functions. The porosity of the mesh 600 may alsobe generated to provide impedance to blood flow dynamics so as to allowthe natural blood clotting mechanism take over to close off theaneurysm.

An outer Titanium atomized layer deposited on the surface of thin filmmesh 600 may act as a passivation layer to enhance biocompatibility, or,other surface passivation processes may be used as needed depending onthe nature and composition of the mesh structure 600.

Thermomechanical properties of the thin film mesh structure 600 alsoplay an important part of overall implant performance. While anyengineering material suitable for permanent implantation may be aconstituent comprising the mesh, one particularly suitable material isNiTi. Mesh 600 may be comprised of NiTi in a martensitic phase,austenitic phase, or a phase mixed between the two, or may be amultilayer of several NiTi film compositions. In some embodiments theNiTi thin film may be combined in a multilayer structure with otheracceptable biocompatible metals including, but not limited to,biocompatible stainless steel, tantalum, tungsten, titanium, or platinumor combinations or multilayers.

In some embodiments, the mesh 600 of an implant is substantially orpredominantly in the austenitic phase so as to provide the bestsuperelasticity and load carrying strength. The greater the differencebetween body temperature and the temperature at which an implant and thestructure of mesh 600 transform into the austenitic stage, the “Aftemperature”, and the greater the stiffness of the mesh 600. However,with increased stiffness come tradeoffs in fatigue resistance.Therefore, an optimized structure of mesh 600 offers a good combinationof thermomechanical properties and mesh geometry to allow for localizeddistortions during expansion during and after deployment in situ, duringmanufacturing manipulations, and during catheterized delivery throughtortuous vasculature. Af temperatures may range from 10 degrees Celsiusto 37 degrees Celsius. The film thickness can be in a range from 1micron to 200 microns, with a preferable range of about 6 microns toabout 12 microns, wherein the thickness is a factor in the outward forceand the controlled resistance to compression forces of the appliedradial pressure from the blood vessel, a factor in catheter profile, andthe like.

The mesh structure 600 of FIGS. 6A and 6B is comprised of a series ofarc-like shaped struts 602 connected at a central node 601 thatcollectively form a “pinwheel”. The plurality of struts 602 form a unitcell pinwheel structure that is capable of expansion or contraction. Inthe instant example, the unit cells of mesh 600 are interconnected by aplurality of secondary nodes 603 that are formed by the intersection ofstruts 602 of adjacent cells. Thus each unit cell of 600 is connected toan adjacent cell via secondary node 603. The roughly hexagonal shape ofthe unit cells of mesh 600 allow for a dense packing factor. Theexpansion or contraction of unit cells induces a rotational deflectionthat causes struts 602 to either expand or contract about central node601 allowing the mesh 600 to have a high capacity for dimensionalgrowth, shrinkage, and localized distortion while maintain a high degreeof uniformity and density.

Alternately, and referring now to FIGS. 7A-7D, a simple perforated mesh700 pattern such as the one shown may be employed. In this exemplarembodiment, a symmetrically repeating plurality of struts 701 areconnected to adjacent struts 701 by nodes 702. FIG. 7(a) shows mesh 700in a generally unexpanded state while FIG. 7(b) shows the same mesh 700in an expanded state where the plurality of struts 701 and plurality ofnodes 702 form a substantially diamond-shaped unit cell. The dimensionsof struts 701, nodes 702, and their resultant unit cells may beoptimized to provide for the most desired mechanical and porositycharacteristics; a variation in the geometry of mesh 700 is shown inFIGS. 7C (unexpanded) and 7D (expanded), the mesh being elongated in onedimensional direction so as to allow for greater expansion and reducedporosity. An optional additional feature for any of the meshes of thepresent disclosure is an eyelet or “tab” such as the general exampleshown by element 703. Tab 703 may be used to convenience duringmanufacturing manipulation, for attachment of radiopaque markers, as asacrificial surface for joining by welding, as a marker visible in theimplantation procedure by x-ray or other methods for placement andlocation confirmation, and the like.

Any of the embodiments described herein may include radiopaque markerbands that can be made from tantalum, titanium or precious metal andplaced on the occluder at any specific location where an eyelet ornodule is formed by the thin film process or configuring the thin filminto a thicker section then the standard wall thickness. The marker maybe crimped, swaged, fused or adhered to the eyelet or the frame based onthe optimum location for the identification of placement of the occludein the body by x-ray (fluoroscopy). The marker may also be plated ontothe specific location or dip plated to ensure the patency of a specificarea of the Occluder is visible under fluoroscopy. Alternatively,radiopacity may be achieved by adding high brightness metals either as asurface coating or by inclusion into a multilayer structure in suchamounts that do not compromise the shaping of the material into desired3 dimensional forms or its mechanical robustness as required forsuccessful deployment.

The occluder shall be sized based on the fluoroscope sizing and then theappropriate size for treatment shall selected by the neurovascularsurgeon. The device shall be preloaded with the specific occlude andsterilized by means of gamma, e-beam or ETO, without impacting theoverall device capability for a one-time-use and achieving thetrackability to the specific location without any friability to thedelivery system or the occlude. Once in position, confirmed by theneurovascular surgeon by fluoroscopy, the center delivery wire can bemanipulated by torque and axial pushing to ensure the delivery systemtip is at the neck of the aneurysm area. The release shall be completedby moving the inner delivery wire distally, or by moving the outersheath proximally or by both at the same time. The occluder shall changefrom the configured loaded shape to the final configured shape partiallyas it exits the sheathed state but will achieve its final shape oncefully released from the delivery system.

FIGS. 13A-13D show another embodiment of an occlusion device 1300 thatis configured to transition between a first, two-dimensionalconfiguration (see FIG. 13A) and a second, three-dimensionalconfiguration (see FIG. 13D). In some configurations, the occlusiondevice can be constructed from thin-film nitinol.

The occlusion device includes a mesh structure having a porosity 1318with a substantially uniform or uniform pore size (see FIG. 13C). Anysingle pore size can be within at least about 5% of a pore size of anyother pore or the mean pore size. The size of the perforation holes andthe dimensions of the supporting mesh are chosen to maximize theocclusive performance in the device while maintaining sufficientstructural strength to enable handling and deployment of the devicewithout tearing.

In the first configuration, the occlusion device 1300 is in a flat,planar configuration with parallel surfaces. At rest, the occlusiondevice 1300 has a substantially uniform or uniform thickness, forexample, a thickness of the occlusion device 1300 is at least about 0.2mils and/or less than or equal to about 2.0 mils, such as between about0.5 mils to about 1.5 mils or between about 1.0 mils to about 2.0 mils.

As shown in FIG. 13A, the occlusion device 1300 extends from a first endportion 1302 to a second end portion 1304. The occlusion device caninclude one or more petals or segments 1314 a-1314 d (e.g., at leasttwo, at least three, at least four, or more) extending along alongitudinal axis of the occlusion device 1300. The one or more segments1314 a-1314 d can be arranged such that a longitudinal axis of each ofthe one or more segments 1314 a-1314 d extends along a longitudinal axisof the occlusion device 1300.

A length of each segment 1314 a-1314 d can be greater than a width ofthe respective segment 1314 a-1314 d. The length of each segment 1314a-1314 d can be at least about 1.5×, at least about 2.0×, at least about2.5×, or at least about 3.0× greater than the width of the respectivesegment 1314 a-1314 d.

One or more of the segments 1314 a-1314 d can be the same size and/or bedifferently sized from one or more other segments 1314 a-1314 d. Forexample, in some configurations, the segments 1314 a-1314 d can be thesame size. In other configurations, each of the segments can bedifferently sized. In yet other configurations, a subset of the segmentscan be differently sized from another subset of the segments.

For example, as shown in FIG. 13A, segments 1314 a, 1314 d can be largerthan segments 1314 b, 1314 c. Smaller segments 1314 b, 1314 c can bepositioned longitudinally between larger segments 1314 a, 1314 d. Thelength and/or width of segments 1314 a, 1314 d can be greater than thelength and/or width of segments 1314 b, 1314 c. As shown, the lengthsand the widths of segments 1314 a 1314 d are greater than the lengthsand the widths of segments 1314 b, 1314 c.

The length and/or width of each segment 1314 a-1314 d can be greaterthan the length and/or width of first and/or second end portions 1302,1304. As shown, a length and width of each segment 1314 a-1314 d isgreater than the length and width of first and second end portions 1302,1304.

The occlusion device 1300 can be formed as a monolithic structure witheach of the segments 1314 a-1314 d joined by connecting portions 1306.The length and/or width of each segment 1314 a-1314 d can be greaterthan the length and/or width of each connecting portions 1306.

The occlusion device can include reinforcing portions with no porosityto provide smooth edges and structural support. The reinforcing portionscan have the same thickness as the porous portions of the occlusiondevice. The reinforcing portions can be monolithically formed with theporous portions.

The occlusion device can have peripheral reinforcing portions 1308,horizontal reinforcing portions 1310, and/or vertical reinforcingportions 1312. Each reinforcing portion 1308, 1310, 1312 can have awidth of at least about 0.2 mil and/or less than or equal to about 1mil, such as between about 0.2 mil and about 0.5 mil or between about0.5 mil and about 1.0 mil.

Peripheral reinforcing portions 1308 can extend at least partially orentirely around a periphery of the occlusion device 1300. A horizontalreinforcing portion 1310 can extend at least partially or entirelyacross the longitudinal axis of the occlusion device 1300. One or morevertical reinforcing portions 1308 can extend perpendicular to thelongitudinal axis of the occlusion device 1300. For example, a verticalreinforcing portion 1308 can extend across a central axis of a segment(see e.g., segments 1314 a, 1314 c, 1314 d), or multiple verticalreinforcing portions 1308 can extend parallel to each other in a singlesegment (see, e.g., segment 1314 b).

Optionally, the occlusion device 1300 can have one or more holes 1316for use as grommets to facilitate attachment of support wires or otherstructures for delivery. Each hole 1316 can be centered on a horizontalreinforcing portion 1310 and/or vertical reinforcing portion 1308. Eachof the holes 1316 can have a larger open area than a pore of the porousportion 1318.

The occlusion device 1300 can be shape-set such that the occlusiondevice 1300 can transition from the two-dimensional configuration to thethree-dimensional configuration. In the three-dimensional configuration,the occlusion device 1300 forms a volumetric filler. As shown in FIG.13D, the occlusion device 1300 can spiral to form a cylindrical formwith open ends.

When transformed from the two-dimensional configuration to thethree-dimensional configuration, the pore size or open area of each porein the three-dimensional configuration changes less than 20% (or lessthan 15%, or less than 10%, or less than 5%) than the pore size or openarea of the same pore in the two-dimensional configuration. In each ofthe two-dimensional and three-dimensional configurations, there is lessthan 20% (or less than 15% or less than 10% or less than 5%) variationbetween the pore size or open area of any two openings. In each of thetwo-dimensional configuration and the three-dimensional configuration,there is less than 20% (or less than 15% or less than 10% or less than5%) variation or between the pore size of any opening and the mean poresize of the entire porosity. In some configurations, every pore andopening has a uniform size in the two-dimensional configuration and/orthree-dimensional configuration.

The surface area of a surface (one side) of the implant can be at least1.5 times greater (or at least 2.0 times greater, or at least 2.5 timesgreater, or at least 3.0 times greater) than an internal volume formedwhen the implant is in the three-dimensional configuration.

FIGS. 14A-14D show yet another embodiment of an occlusion device 1400that is configured to transition between a first, two-dimensionalconfiguration (see FIG. 14A) and a second, three-dimensionalconfiguration (see FIGS. 14C and 14D). In some configurations, theocclusion device can be constructed from thin-film nitinol.

The occlusion device includes a mesh structure having a porosity 1418with a substantially uniform or uniform pore size (see FIG. 14B). Anysingle pore size can be within at least 5% of a pore size of any otherpore or the mean pore size. The size of the perforation holes and thedimensions of the supporting mesh are chosen to maximize the occlusiveperformance in the device while maintaining sufficient structuralstrength to enable handling and deployment of the device withouttearing.

In the first configuration, the occlusion device 1400 is in a flat,planar configuration with parallel surfaces. At rest, the occlusiondevice 1400 has a substantially uniform or uniform thickness. Forexample, a thickness of the occlusion device 1300 can be at least about0.2 mils and/or less than or equal to about 2.0 mils, such between about0.5 mils and about 1.5 mils or between about 1.0 mils and about 2.0mils.

As shown in FIG. 14A, the occlusion device 1400 extends from a first end1402 to a second end 1404. The occlusion device 1400 can include one ormore petals or segments 1414 (e.g., at least two, at least three, atleast four, or more) connected end-to-end. The one or more segments 1414may be arranged such that segments are arranged at an angle with respectto adjacent segments. However, in other configurations, a longitudinalaxis of each segment 1414 can extend along a longitudinal axis of theocclusion device 1400.

A length of each segment 1414 can be greater than a width of therespective segment 1414. The length of each segment 1414 can be at leastabout 1.5×, at least about 2.0×, at least about 2.5×, or at least about3.0× greater than the width of the respective segment 1414.

As shown, each of the segments 1414 is the same size with equal lengthsand widths. However, in other configurations, one or more of thesegments 1414 can be differently sized from one or more other segments1414.

The occlusion device 1400 can be formed as a monolithic structure witheach of the segments 1414 joined to an adjacent segment. Optionally, theocclusion device 1400 can include a hole or grommet 1416 at a transitionbetween adjacent segments. Each of the holes 1416 can have a larger openarea than a pore of the porous portion 1418. The holes 1416 can be usedto facilitate attachment to support wires or other structures fordelivery.

The occlusion device 1400 can include reinforcing portions with noporosity to provide smooth edges and structural support. The reinforcingportions can have the same thickness as porous portions of the occlusiondevice. The reinforcing portions can be monolithically formed with theporous portions.

The occlusion device can have peripheral reinforcing portions 1408,horizontal reinforcing portions 1410, and/or vertical reinforcingportions 1412. Each reinforcing portion 1408, 1410, 1412 can have awidth of at least about 0.2 mil and/or less than or equal to about 1mil, such as between about 0.2 mil and about 0.5 mil or between about0.5 mil and about 1.0 mil.

Peripheral reinforcing portions 1408 can extend at least partially orentirely around a periphery of the occlusion device 1400. A horizontalreinforcing portion 1410 can extend at least partially or entirelyacross the longitudinal axis of one or more segments 1414. One or morevertical reinforcing portions 1408 can extend perpendicular to thelongitudinal axis of one or more segments 1414. For example, a verticalreinforcing portion 1418 can extend across a central axis of eachsegment 1414.

The occlusion device 1400 can be shape-set such that the occlusiondevice 1400 can transition from the two-dimensional configuration to thethree-dimensional configuration. As shown in FIGS. 14C and 14D, theocclusion device 1400 can include a closed portion 1420 and an openportion 1422. The occlusion device 1400 can fold such that alongitudinal dimension of each segment can extend from one side of theopen portion 1422 and around to the other side of the open portion 1422to form the closed portion 1420. The open portion 1422 can be formed bythe longitudinal edges of two adjacent segments (see FIG. 14C). Whencompletely folded, adjacent longitudinal edges of segments 1414 overlapeach other such that there are no gaps between adjacent segments 1414(see FIG. 14D).

When transformed from the two-dimensional configuration to thethree-dimensional configuration, the pore size or open area of each porein the three-dimensional configuration changes less than 20% (or lessthan 15%, or less than 10%, or less than 5%) than the pore size or openarea of the same pore in the two-dimensional configuration. In each ofthe two-dimensional configuration and the three-dimensionalconfiguration, there is less than 20% (or less than 15% or less than 10%or less than 5%) variation between the pore size or open area of any twoopenings. In each of the two-dimensional configuration and thethree-dimensional configuration, there is less than 20% (or less than15% or less than 10% or less than 5%) variation or between the pore sizeof any opening and the mean pore size of the entire porosity. In someconfigurations, every pore and opening has a uniform size in thetwo-dimensional configuration and/or three-dimensional configuration.

The surface area of a surface (one side) of the implant can be at least1.5 times greater (or at least 2.0 times greater, or at least 2.5 timesgreater, or at least 3.0 times greater) than an internal volume formedwhen the implant is in the three-dimensional configuration.

When implanted, the open portion 1422 can face the aneurysm neck suchthat blood can flow into the internal volume formed by the closedportion 1420. In some embodiments, fillers (e.g., coils) can be releasedin the internal volume of the occlusion device 1400.

Although certain embodiments have been described herein with respect toneurovascular aneurysms, the devices described herein can be used totreat other types of aneurysms, e.g. aortic aneurysms, ventricularaneurysms, etc.

As used herein, the relative terms “proximal” and “distal” shall bedefined from the perspective of the delivery system. Thus, proximalrefers to the direction of the handle portion of the delivery system anddistal refers to the direction of the distal tip.

Conditional language, such as “can,” “could,” “might,” or “may,” unlessspecifically stated otherwise, or otherwise understood within thecontext as used, is generally intended to convey that certainembodiments include, while other embodiments do not include, certainfeatures, elements, and/or steps. Thus, such conditional language is notgenerally intended to imply that features, elements, and/or steps are inany way required for one or more embodiments.

The terms “comprising,” “including,” “having,” and the like aresynonymous and are used inclusively, in an open-ended fashion, and donot exclude additional elements, features, acts, operations, and soforth. Also, the term “or” is used in its inclusive sense (and not inits exclusive sense) so that when used, for example, to connect a listof elements, the term “or” means one, some, or all of the elements inthe list.

Although certain embodiments and examples have been described herein, itwill be understood by those skilled in the art that many aspects of thedelivery systems shown and described in the present disclosure may bedifferently combined and/or modified to form still further embodimentsor acceptable examples. All such modifications and variations areintended to be included herein within the scope of this disclosure. Awide variety of designs and approaches are possible. No feature,structure, or step disclosed herein is essential or indispensable.

For purposes of this disclosure, certain aspects, advantages, and novelfeatures are described herein. It is to be understood that notnecessarily all such advantages may be achieved in accordance with anyparticular embodiment. Thus, for example, those skilled in the art willrecognize that the disclosure may be embodied or carried out in a mannerthat achieves one advantage or a group of advantages as taught hereinwithout necessarily achieving other advantages as may be taught orsuggested herein.

Moreover, while illustrative embodiments have been described herein, thescope of any and all embodiments having equivalent elements,modifications, omissions, combinations (e.g., of aspects across variousembodiments), adaptations and/or alterations as would be appreciated bythose in the art based on the present disclosure. The limitations in theclaims are to be interpreted broadly based on the language employed inthe claims and not limited to the examples described in the presentspecification or during the prosecution of the application, whichexamples are to be construed as non-exclusive. Further, the actions ofthe disclosed processes and methods may be modified in any manner,including by reordering actions and/or inserting additional actionsand/or deleting actions. It is intended, therefore, that thespecification and examples be considered as illustrative only, with atrue scope and spirit being indicated by the claims and their full scopeof equivalents.

The ranges disclosed herein also encompass any and all overlap,sub-ranges, and combinations thereof. Language such as “up to,” “atleast,” “greater than,” “less than,” “between,” and the like includesthe number recited. Numbers preceded by a term such as “about” or“approximately” include the recited numbers and should be interpretedbased on the circumstances (e.g., as accurate as reasonably possibleunder the circumstances, for example ±1%, ±5%, ±10%, ±15%, etc.). Forexample, “about 100 microns” includes “100 microns.” Phrases preceded bya term such as “substantially” include the recited phrase and should beinterpreted based on the circumstances (e.g., as much as reasonablypossible under the circumstances). For example, “substantially uniform”includes “uniform.”

EXAMPLE EMBODIMENTS

The following example embodiments identify some possible permutations ofcombinations of features disclosed herein, although other permutationsof combinations of features are also possible.

-   -   1. An occlusion device comprising:        -   a mesh structure comprising a first surface and a second            surface, at least a portion of the mesh structure comprises            porosity, the mesh structure being configured to transition            between a two-dimensional configuration and a            three-dimensional configuration,        -   wherein in the two-dimensional configuration and at rest,            the first surface is parallel to the second surface, and        -   wherein in the three-dimensional configuration, the            occlusion device comprises an internal volume.    -   2. The occlusion device of Embodiment 1, wherein the mesh        structure is a monolithic sheet.    -   3. The occlusion device of Embodiment 1 or 2, wherein the mesh        structure comprises a thickness of no more than 0.002 inches.    -   4. The occlusion device of any one of Embodiments 1 to 3,        wherein in the three-dimensional configuration, the occlusion        device is at least partially spherical.    -   5. The occlusion device of any one of Embodiments 1 to 3,        wherein in the three-dimensional configuration, the occlusion        device is at least partially cylindrical.    -   6. The occlusion device of any one of the preceding Embodiments,        wherein the mesh structure comprises a uniform thickness.    -   7. The occlusion device of any one of the preceding Embodiments,        wherein a surface area of the first surface is at least 2×        greater than the internal volume.    -   8. The occlusion device of Embodiment 7, wherein the surface        area of the first surface is at least 3× greater than the        internal volume.    -   9. The occlusion device of any one of the preceding Embodiments,        wherein the mesh structure comprises a reinforcing portion with        no porosity.    -   10. The occlusion device of Embodiment 9, wherein the        reinforcing portion extends around a periphery of the mesh        structure.    -   11. The occlusion device of Embodiment 10, wherein the        reinforcing portion extends around the entire periphery of the        mesh structure.    -   12. The occlusion device of any one of the preceding        Embodiments, wherein in the three-dimensional configuration, the        occlusion device has an open portion to provide access to the        internal volume.    -   13. The occlusion device of any one of the preceding        Embodiments, wherein in the two-dimensional configuration, the        entire porosity has a uniform pore size.    -   14. The occlusion device of any one of the preceding        Embodiments, wherein in the two-dimensional configuration, any        pore size of the porosity is within 10 percent of a first mean        pore size of the entire porosity of the two-dimensional        configuration.    -   15. The occlusion device of Embodiment 14, wherein in the        two-dimensional configuration, any pore size of the porosity is        within 5 percent of the first mean pore size.    -   16. The occlusion device of any one of the preceding        Embodiments, wherein in the three-dimensional configuration, any        pore size of the mesh structure is within 10 percent of a second        mean pore size of the entire porosity of the two-dimensional        configuration.    -   17. The occlusion device of Embodiment 16, wherein a first pore        size of any pore in the two-dimensional configuration is within        5 percent of a second pore size of the same pore in the        three-dimensional configuration.    -   18. The occlusion device of any one of the preceding        Embodiments, wherein in the three-dimensional configuration, the        mesh structure is partially austenitic and partially        martensitic.    -   19. The occlusion device of claim 18, wherein the mesh structure        is more austenitic than martensitic.    -   20. The occlusion device of any one of the preceding        Embodiments, further comprising a volumetric filler disposed in        the internal volume of the mesh structure.    -   21. The occlusion device of Embodiment 20, wherein the mesh        structure comprises the volumetric filler.    -   22. An occlusion device comprising:        -   a monolithic structure comprising porosity, the monolithic            structure being configured to transition between a first            configuration and a second configuration,        -   wherein in the first configuration, any pore size of the            porosity is within 10 percent of a first mean pore size of            the entire porosity of the first configuration;        -   wherein in the second configuration, any pore size of the            porosity is within 10 percent of a second mean pore size of            the entire porosity of the second configuration.    -   23. The occlusion device of Embodiment 22, wherein the        monolithic structure is a monolithic sheet.    -   24. The occlusion device of Embodiment 22 or 23, wherein the        monolithic structure comprises a thickness of no more than 0.002        inches.    -   25. The occlusion device of any one of Embodiments 22 to 24,        wherein in the second configuration, the occlusion device is at        least partially spherical.    -   26. The occlusion device of any one of Embodiments 22 to 24,        wherein in the second configuration, the occlusion device is at        least partially cylindrical.    -   27. The occlusion device of any one of Embodiments 22 to 26,        wherein in the three-dimensional configuration, the occlusion        device has an open portion to provide access to the internal        volume.    -   28. The occlusion device of any one of Embodiments 22 to 27,        wherein the monolithic structure comprises a uniform thickness.    -   29. The occlusion device of any one of Embodiments 22 to 28,        wherein a surface area of the first surface is at least 2×        greater than the internal volume.    -   30. The occlusion device of Embodiment 29, wherein the surface        area of the first surface is at least 3× greater than the        internal volume.    -   31. The occlusion device of any one of Embodiments 22 to 30,        wherein the monolithic structure comprises a reinforcing portion        with no porosity.    -   32. The occlusion device of Embodiment 31, wherein the        reinforcing portion extends around a periphery of the mesh        structure.    -   33. The occlusion device of Embodiment 32, wherein the        reinforcing portion extends around the entire periphery of the        mesh structure.    -   34. The occlusion device of any one of Embodiments 22 to 33,        wherein a first pore size of any pore in the first configuration        is within 5 percent of a second pore size of the same pore in        the second configuration.    -   35. The occlusion device of any one of Embodiments 22 to 34,        wherein in the two-dimensional configuration, any pore size of        the mesh structure is within 5 percent of the first mean pore        size.    -   36. The occlusion device of any one of Embodiments 22 to 35,        wherein in the three-dimensional configuration, any pore size of        the mesh structure is within 5 percent of the second mean pore        size.    -   37. The occlusion device of any one of Embodiments 22 to 36,        wherein in the first configuration, the porosity has a uniform        pore size.    -   38. The occlusion device of any one of Embodiments 22 to 37,        wherein in the second configuration, the mesh structure is        partially austenitic and partially martensitic.    -   39. The occlusion device of Embodiment 38, wherein the mesh        structure is more austenitic than martensitic.    -   40. The occlusion device of any one of Embodiments 22 to 39,        further comprising a volumetric filler disposed in the internal        volume of the mesh structure.    -   41. The occlusion device of Embodiment 40, wherein the mesh        structure comprises the volumetric filler.    -   42. A method of deploying an occlusion device, the method        comprising:        -   releasing the occlusion device from a catheter and into an            aneurysm sac, the occlusion device comprising:            -   a mesh structure having porosity,            -   a first configuration in which the occlusion device is                planar, and            -   a second configuration in which the occlusion device is                partially folded, wherein when the occlusion device is                in the catheter, the occlusion device is in the second                configuration; and        -   transforming the occlusion device from the second            configuration to a third configuration in which the            occlusion device comprises an internal volume;        -   wherein a first pore size of any pore in the first            configuration is within 5 percent of a second pore size of            the same pore in the second configuration.    -   43. The method of Embodiment 42, further comprising filling the        internal volume of the occlusion device with a volumetric        filler.    -   44. The method of Embodiment 43, wherein filling the internal        volume comprises folding a portion of the mesh structure into        the internal volume of the occlusion device.    -   45. The method of any one of Embodiments 42 to 44, wherein in        the first configuration, the mesh structure comprises a uniform        pore size.    -   46. The method of any one of Embodiments 42 to 45, wherein in        the third configuration, the occlusion device is at least        partially spherical.    -   47. The method of any one of Embodiments 42 to 45, wherein in        the third configuration, the occlusion device is at least        partially cylindrical.    -   48. The method of any one of Embodiments 42 to 47, the mesh        structure comprises a monolithic sheet.

1. (canceled)
 2. A method of deploying an occlusion device, the methodcomprising: advancing a delivery system carrying the occlusion device toa primary vessel, wherein when the occlusion device is in the deliverysystem, the occlusion device is in a delivery configuration in which theocclusion device is partially folded; releasing the occlusion devicefrom the delivery system and into an aneurysm sac, the occlusion devicecomprising: a monolithic sheet comprising a mesh structure havingporosity; and transforming the occlusion device from the deliveryconfiguration to an implanted configuration in which the occlusiondevice comprises an internal volume, wherein a first pore size of anypore in a planar configuration is within 5 percent of a second pore sizeof the same pore in the delivery configuration.
 3. The method of claim2, further comprising filling the internal volume of the occlusiondevice with a volumetric filler.
 4. The method of claim 3, whereinfilling the internal volume comprises folding a portion of the meshstructure into the internal volume of the occlusion device.
 5. Themethod of claim 2, wherein in the planar configuration, the meshstructure comprises a uniform pore size.
 6. The method of claim 2,wherein in the implanted configuration, the occlusion device is at leastpartially spherical.
 7. The method of claim 2, wherein in the implantedconfiguration, the occlusion device is at least partially cylindrical.8. The method of claim 2, wherein the monolithic sheet further comprisesa reinforcing portion comprising no porosity.
 9. The method of claim 8,wherein the reinforcing portion extends around an outer edge of the meshstructure.
 10. The method of claim 8, wherein the mesh structurecomprises a plurality of rounded segments connected end-to-end.
 11. Themethod of claim 10, wherein the reinforcing portion extends across acentral axis of each of the plurality of rounded segments.
 12. Themethod of claim 10, wherein each of the plurality of rounded segmentshas a length along a major axis and a width along a minor axis, thelength being greater than the width.
 13. The method of claim 10, whereinthe reinforcing portion further comprises a horizontal reinforcingportion extending across a major axis of each of the plurality ofsegments.
 14. The method of claim 13, wherein the reinforcing portionfurther comprises a vertical reinforcing portion extending across aminor axis of each of the plurality of segments.
 15. The method of claim13, wherein in the implanted configuration, adjacent longitudinal edgesof the plurality of rounded segments overlap.
 16. The method of claim 2,wherein the pore size of any pore of the mesh structure in the implantedconfiguration changes less than 20% than the pore size of the same porein the delivery configuration when transforming the occlusion devicefrom the delivery configuration to the implanted configuration.
 17. Themethod of claim 2, wherein the mesh structure comprises a uniformthickness.
 18. The method of claim 2, wherein in the implantedconfiguration, the occlusion device has an open portion to provideaccess to the internal volume, the method further comprising releasingthe occlusion device into the aneurysm sac such that the open portionfaces a neck of the aneurysm sac.
 19. The method of claim 2, wherein themesh structure is partially austenitic and partially martensitic. 20.The method of claim 2, wherein releasing the occlusion device from thedelivery system comprising retracting a sheath covering the occlusiondevice.
 21. The method of claim 2, further comprising retaining theocclusion device in the delivery system by an interference fit betweenthe occlusion device and an inner push rod.